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Aging is a software bug

In my review of the movie Tomorrowland, I alluded to the fact that in the alternate world, people could stay young by drinking orange juice every morning. I conjectured that this was probably caused by nanotechnology.

I do not expect to ever drink some orange juice that keeps me young… but wouldn’t that be nice?

Someone accused me of being a follower of Ray Kurzweil. I had vaguely heard of Kurzweil as someone who advocates that, soon, computers will exceed the computational power of the human mind. Seems reasonable enough to me.

In any case, I went back and read some of Kurzweil’s work. It turns out that he does predict the arrival of nanotechnology-based rejuvenation. He even put a date to it: in 20 years, or around 2035. And after that point, forever youth could become reality.

One should point out that we cannot really defeat death. The best we could do is defeat aging: death as the result of an accident or a new disease is really hard to prevent, even in theory.

I do not believe that, currently, there is much you can do to extend your lifespan beside the usual if you are already healthy: keep your weight in check, exercise, have a loving family, don’t get mad at your collaborators… So, if you are healthy, do not bother looking for some magical orange juice. It is also not going to be easy to drastically extend our lifespan. If there was some simple herb that could rejuvenate us, the word would have gotten out by now. Moreover, if you could just flip a gene and live forever, we would have documented cases by now: there are billions of us… it is likely that one of us would have gotten the lucky mutation.

But Kurzweil believes that human technology is much stronger than mere luck.

By 2035, Kurzweil will have far exceeded men’s life expectancy (he will get close to 90). He has a plan to get there by closely monitoring his health and taking a crazy amount of supplements. That does not sound insane: if someone puts his mind to it, I am not sure why he cannot drastically increase his probability of living till late in his 80s.

Back to his predictions. It is evident that the rate of progress grows every year. If you must have a metric, look at the number of research articles published every year: it has consistently grown by more than 2% a year for as far back as I can look. By a small but consistent growth of about 3.5% a year, we went (in the US alone) from 110k medical research papers a year in 1996 to 200k in 2013. (This does not account for the fact that China hardly published anything in 1996 while it published 50k medical papers in 2013.) We get such progress because our tools get better and relatively cheaper every year while our collective expertise grows. Kurzweil says that to predict the amount of progress we shall make in the next 20 years, we must not simply project the progress of the past on the future, but rather multiply it. The farther you look, the wider the gap grows between a linear and exponential prediction.

Progress is necessarily unequal. Though we publish more medical papers every year than we ever did, some topics remain poorly researched whereas others are progressing much faster. But with an aging population worldwide, it is a safe bet that aging research is growing faster than medical research at large.

If you are not following closely biotechnology, it is easy to think that there is no much progress. But did you know that we have a relatively safe tool to edit human being genes called CRISPR since 2012? In fact, Chinese researchers are editing the genome of human embryos right now, hoping to prevent diseases. It is a safe bet that someone will soon attempt to raise “super human beings”: e.g., we already know of genetic mutations providing the recipients with superhuman muscles and unbreakable bones, an army of such people sounds like a tempting proposition. At Harvard, they are using this technology, as we speak, to turn an elephant into a mammoth by editing its genes. Did you know that we have commercially available bio 3D printers that can print skin or blood vessels? There is currently a competition to build an artificial liver good enough to keep a large animal alive for 90 days without any support: the competition ends in 2018. If the prize is won, and it will probably be, the next step is to create the other organs. At this rate, it is not hard to believe that, within ten years, we shall be technically able to replace any organ in one’s body, without any need for a human donor or for long-term dangerous medications.

Still. I have looked at Kurzweil predictions a bit more closely, and they seem a bit overoptimistic. I would say that you should probably add 10 years to all his dates. So, if Kurzweil was to predict that we would defeat aging in 30 or 40 years (in 2045 or 2055), then I would say that this is credible. If we go back 40 years ago, medicine was far, far less advanced. The rate of deaths from major diseases was often twice what it is today. If we project in the future several times the progress of the last 40 years, it is hard to imagine what we cannot do.

There is a problem with these predictions, of course. At the moment, we do not even know what aging is. Not really. We know that lobsters and naked mole rats do not age (they die but not because of an aging process similar to ours). The jellyfish and hydra are “immortal”. Some trees, like the bristlecode pine also do not age. Trees do not appear to age, or rather they age in reverse (getting stronger and more fertile with time), but are physically limited over time by their size (not unlike lobsters). We know that among creatures of the same size, say a mouse and a bat, there can be vast difference in longevities. Different species of sea urchins have reported lifespans ranging from 4 to more than 100 years. For individuals of the same species, big (or taller) individuals live shorter lives. We also know that if you inject the blood plasma of a young mouse in an old mouse (a technique called parabiosis), it rejuvenates the old mouse. But I do not think scientists can explain any of it (not to my satisfaction).

There are various theories about what aging is. Some say it is programmed. We are programmed to age. It does make sense from an evolutionary perspective that we are “programmed” to die after a time. And certainly, women are programmed to reproduce before the age of 40, but not after. This is probably well motivated: e.g, people who die make room for new people with possibly better genetic code…

Another theory is that evolution did its best to maximize our lifespan, and we have the very best we can get… short of becoming androids. But there is no reason to believe that evolution would seek to maximize our lifespan. The cycle of birth, reproduction and death works well for evolution. Evolution does not care for the individual, only for the species.

I have also revisited Aubrey de Grey who has this ambitious plan to defeat aging using advanced regenerative medicine. He believes that aging is the result of “accumulated damage”. To him, our bodies are like rusting cars. Evidently, our bodies break down as they age… but why would a mouse accumulate damage 30 times faster than a human being? Why would it accumulate damage 8 times faster than a bat? And how come a whale or a turtle can live much older than us: aren’t they damaged? Some of aging is definitively accumulated damage… your teeth become shorter as you grow older, you accumulate latent viruses, fat cells, you lose neurons in the neocortex (and, in human beings, they are not replenished)… but male baldness is not a random outcome due to damage. Working out damages your body, yet it also improves your health, even in old age. This means that your body does not activate all of its self-repair mechanisms.

So aging is not solely a matter of “damage” (as in an old car). That is not to say that de Grey is wrong… I believe that he is right and I have given out some of my own money to his foundation. But I am not sure the analogy between a car and the human body is best.

My own theory, after reading avidly on the topic for several days, is that we are like a piece of software designed in 1970 and still running three decades later… we are hitting various “year 2000 bugs“. Evolution did not try to maximize our life expectancy (as it may have done with turtles and some whales). If anything, evolution is glad we do not often live beyond 90.

It seems to me that the easiest way to live longer would be to hack our own software (our genome, our biome) as well as repairing various sources of damages (e.g., using stem cells). Sadly, as I have pointed out, it cannot be a simple matter of turning on one gene or the other. Software programmers know all too well how hard it can be to fix what might appear like a minor adjustment… Some bugs can be fixed by changing a few lines, but some require rewriting entire code segments. To turn the clock, we will need some fancy engineering.

What is this clock? There is some hope that the clock in question could be our telomeres. It is an apparently frivolous part of your DNA that grows shorter with every cell division. So it would seem like simply making the telomere longer could make us somewhat younger again. Thankfully, we know how to do just that using telomerase. De Jesus et al. showed that telomerase gene therapy in old mice delays aging and increases longevity without increasing cancer. So, maybe, if we could replenish our telomeres without killing ourselves, we could fool our body into thinking it is younger. It seems that people who live very old without cancer or Alzheimer’s are more likely to have a rare mutation that activates telomerase production. But there is no guarantee that it would work. For one thing, some cells do produce telomerase (e.g., the white cells) and their telomeres still grow short in some people. For another, we know that some cells rarely multiply and are thus unlikely to be limited by telomeres (e.g., your neurons). Moreover, eating well and exercising can extend your telomeres in some cells, though it evidently does not make you younger. There are other possible biological clocks such as DNA methylation. We really do not know enough about what makes a cell old!

It is not just your cells that get old. The tissues themselves (like your skin) fail to repair themselves properly with age. You can see wrinkles in people over 40. We also accumulate lots of broken protein that go on to contribute to Alzheimer’s, Parkinson’s and plenty of other diseases.

Still, I believe that telomeres elongation of some specific cells (with or without telomerase) coupled with advanced stem cell therapy and/or a few well-dosed hormones and proteins could probably rejuvenate you, maybe. For example, a simple, freely available, hormone, oxytocin can rejuvenate muscles. But it is also possible, even likely, that it is much more complicated, even assuming that I got everything right.

One can dream. I imagine that, in the future, you will live normally as human being until you are about 40 (when reproduction normally stops) at which point, you will start taking pills, or injections or nanobots, to make your body believe that you are still 30. There will be some wear and tear, as indicated by de Grey, but it won’t be a big problem. Using 3D printers, we shall be able to print new body parts out of our stem cells. Or, better yet, we will get in situ regeneration. You would need to replenish the neurons in your neocortex every few decades.

When that happens, be ready to work for 60 years or more! (Assuming that people still need to work in the future…)

Unfortunately, there seems to be less research on this important question that you may think. For example, there is a compound that is FDA approved (rapamycin) that is believed to extend lifespans of mammals through some gene hacking. Since we are already giving it to some human beings, you would think that we would have tested it on all mammals by now. Sadly no. There is a project to use it on dogs however, but I do not know whether they got funded.

(Do not go out on the black market to buy rapamycin. It has nasty side effects and it would, at best, delay aging… not reverse or stop it. Plus, it appears to be a telomerase inhibitor so it could actually make your telomeres shorter… and give you cancer and diabetes…)

Unfortunately, we will not defeat aging in the next ten years I would think (short of a surprising, 1 in a million, breakthrough). For one thing, “defeating aging” is not yet a socially acceptable goal. It is a taboo. We do not know what aging is. We have no proven means right now to extend human lifespan. You can probably help your chances of making it to 80, but there is nothing you can do to get beyond 125.

To have any realistic chance at defeating aging in ten years, we would need to have done it, right now, in a few people or in a mouse. To have a realistic chance of doing it in 20 years, we would need to have an excellent plan right now. Maybe someone has such a plan right now… it is hard to tell… given the profit involved, they might not freely share their plan… de Grey has such a plan, but he will only commit to a 25-year schedule on the condition that he has a billion dollars… yet he does not have a billion dollar.

But there are reasons to be hopeful. Google, of all places, created a company with the express goal of extending our healthspan by 20 to 100 years: Calico. It is not just a silly thing: they have recruited the best scientists that money could buy. Calico has hundreds of millions of dollars with commitments exceeding a billion dollars. Calico is hardly alone: Unity Biotechnology is another well-funded technology company that seeks to “cure aging” (it is backed by Amazon’s CEO) . If you want to be optimistic, you could imagine that Calico or some other laboratory could have, right now, a viable plan to put a dent in aging. If, they could be testing it in human beings in 20 years, and it could be ready for the rest of us in 30 years.

So, let me come up with a prediction: we will defeat aging in 40 years. By that I mean that age-related disease would be mostly under control, if not outright eliminated. So maybe you still get Alzheimer’s or a heart condition, but medical therapies are so good that you can go on living a happy and productive life. Compared to Kurzweil, I am pessimistic (he predicts 20 years or less.)

Speaking for myself, I expect to be dead in 40 years… if nothing changes. I do not think any man in my family has made in his eighties… So if I do not die of something else first, I can expect to die from an age-related disease in my seventies or sooner: cancer, Alzheimer’s, heart attack… Even if I were to survive that long, I fear I would be severely diminished…

There is, however, a small probability that I could have a very different life. For one thing, maybe Kurzweil is right and we will defeat aging in 20 years. I stand a good chance of making it there. That sounds much too optimistic however.

But there is another intriguing possibility popularized by Kurzweil and de Grey. Suppose that we defeat aging layer by layer. Imagine that, in five years, we find a way to rejuvenate old people by 3 years… and then, ten years later, by 5 years… and then ten years later by 7 years… if this were to happen, I am much more likely to make it to my eighties. And by then, it is much more likely that they will be able to reverse my aging. This concept is sometimes called the longevity escape velocity: you do not need to live long enough to see a cure for aging, you just need to live long enough to see partial progress.

Partial progress is much easier than defeating entirely aging. When we will understand better age-related gene expressions, we might be able to tune your “epigenetics” so that it is more youthful simply with a few injections. After all, if parabiosis works, it seems pretty clear that with the right doses of drugs, we could simulate the same effect without requiring a young person’s blood. Such an approach could buy all of us a few extra years. Then if we improve stem cell technology significantly, we might be able to undo other age-related damages. And then maybe we could find a way to elongate our telomeres… after all our body knows how to do it, it simply chooses not to. Successive waves of progress could add up in such a manner.

I have a really hard time imagining that we will still grow old 500 years from now. I do not have a lot of faith in biologists, but there are many of them and they have better and better tools.

But here is something interesting: we never imagine a future where people do not grow old. In Star Trek, James T. Kirk grows old. Even the fierce Vulcans grow old. In Star Wars, people grow old. The only science-fiction author who represented fairly, in my mind, what could happen as we defeat aging through technology is Peter F. Hamilton in his Commonwealth Saga (starting with Pandora’s Star).

We still grant public employees pension plans based on limited longevities. There is a very serious risk that we are grossly underestimating the life expectancy of 20-year-old employees. As far as I can tell, this is never discussed.

I believe that it is because defeating aging by technology is a taboo. Not even science-fiction writers want to consider it. In a sense, it is not surprising that only a few outliers like de Grey and Kurzweil talk about it. Sure, they are probably wrong in many important ways… but they are not wrong in the way that matters: aging can and will be defeated. I expect it is simply a bug in our software: we can reengineer our bodies so that they do not age. You may have to walk around with nanobots in you, but you will not age as long as you are careful.

Let me conclude by quoting Richard Feynman (one of the greatest scientists of the XXth century):

It is one of the most remarkable things that in all of the biological sciences there is no clue as to the necessity of death. If you say we want to make perpetual motion, we have discovered enough laws as we studied physics to see that it is either absolutely impossible or else the laws are wrong. But there is nothing in biology yet found that indicates the inevitability of death. This suggests to me that it is not at all inevitable and that it is only a matter of time before the biologists discover what it is that is causing us the trouble and that this terrible universal disease or temporariness of the human’s body will be cured.

Drug perks up old muscles and aging brains (May 2015): “(…) an Alk5 kinase inhibitor already undergoing trials as an anticancer agent, successfully renewed stem cell function in both brain and muscle tissue of the same old animal, potentially making it stronger and more clever, Conboy said.”

Four Ways to Lengthen Telomeres (May 2015): “At the moment, there are four companies planning human trials to reset telomeres using telomerase genes. In every case, the intent is to put the telomerase genes (hTERT and hTERC) into human patients in an effort to cure age-related diseases.”

Anti-ageing pill pushed as bona fide drug (June 2015): “On 24 June, researchers will try to convince FDA officials that if the trial succeeds, they will have proved that a drug can delay ageing. That would set a precedent that ageing is a disorder that can be treated with medicines, and perhaps spur progress and funding for ageing research.”

32 thoughts on “Aging is a software bug”

I didn’t read everything because I’m quite familiar with all of it. I became aware of these ideas through the idea of “technological singularity”. I like AI a lot and I think it’s going to dramatically change the world for the better, but not that much nor that soon. A few points that I want to make:

– we have accelerating returns and the future progress is underestimated, but so are the challenges. We also have an exponential fiction, the gap between SciFi and science grows exponentially.

– we have additional organizational problems, logistic problems, etc. The acceleration of these returns may not be sustainable, for economic reasons, among many.

– a computer equal in power to the brain is not equal in intelligence. Our software is not there, by far. Strong AI would be a game ender, but it’s not happening anytime soon (in our lifetimes at least)

– among all SciFi themes, I personally like most “mind uploading”. That’s the closest to immortality and eternal youth I can imagine. Additionally, you get the powers of Neo (Matrix) and more, nothing tops that.

– some people say we’re already there, by estimating the likelihood of living in the time before that (a few thousand years of history) vs an eternity of simulation. Or one real year 2015 vs nearly infinite simulated years 2015. I don’t buy that. Main reason: the world is too unfair and random to be designed.

– I like to think all these things are the future (far future, far after quantum computers) but the future depends among other things on the economic interest. See the evolution of smartphones, everybody loves them. Electric cars? Not so much, oil means money, power and influence. We all have interest in a better future, but some people do also have interest on some particular aspects of the present, when these groups of people have money/power/influence they may produce some deceleration to the progress.

– we may still have a chance to get there, cryogenics. The likelihood of successfully restoring someone from cryogenic preservation are zero today. In the future this may change, or it may not. It’s one possibility among an indeterminate number of possibilities, a very large one, a gazillion possibilities. It’s very expensive, and we may already be in a simulation anyway, unlikely, but everything here is.

Most likely: tomorrow will be pretty much like today, and so on every day. I thought we were supposed to have flying cars by 2010. I would like to see wetware connecting directly to human nerves/brain. Cyberpunk, yes, but helpful for many people (e.g. blind people). Still very far in the future as well. Things happen to be not that easy…

– we have accelerating returns and the future progress is underestimated, but so are the challenges. We also have an exponential fiction, the gap between SciFi and science grows exponentially.

Two exponentials can diverge quite quickly. I agree. I think that Kurzweil has a very strong exponential. I think that actual progress is somewhat slower… but it is still much higher than people imagine.

– we have additional organizational problems, logistic problems, etc. The acceleration of these returns may not be sustainable, for economic reasons, among many.

Yes, but the opposite is often true. We see gains that go above and beyond technology alone. For example, the entry of China in the world of science and technology is boosting our worldwide scientific productivity.

– a computer equal in power to the brain is not equal in intelligence. Our software is not there, by far. Strong AI would be a game ender, but it’s not happening anytime soon (in our lifetimes at least)

Anti-aging technology does not depend on strong AI.

– among all SciFi themes, I personally like most “mind uploading”. That’s the closest to immortality and eternal youth I can imagine. Additionally, you get the powers of Neo (Matrix) and more, nothing tops that.

Mind uploading is a distinct issue from anti-aging. It seems like a possible way to defeat death. It is much farther in the future I believe.

– some people say we’re already there, by estimating the likelihood of living in the time before that (a few thousand years of history) vs an eternity of simulation. Or one real year 2015 vs nearly infinite simulated years 2015. I don’t buy that. Main reason: the world is too unfair and random to be designed.

We may be in a simulation. But so what?

– I like to think all these things are the future (far future, far after quantum computers) but the future depends among other things on the economic interest. See the evolution of smartphones, everybody loves them. Electric cars? Not so much, oil means money, power and influence. We all have interest in a better future, but some people do also have interest on some particular aspects of the present, when these groups of people have money/power/influence they may produce some deceleration to the progress.

I could go out and buy an electric car right now. Many of my neighbours have them.

– we may still have a chance to get there, cryogenics. The likelihood of successfully restoring someone from cryogenic preservation are zero today. In the future this may change, or it may not. It’s one possibility among an indeterminate number of possibilities, a very large one, a gazillion possibilities. It’s very expensive, and we may already be in a simulation anyway, unlikely, but everything here is.

Speaking for myself, I do not want to live badly enough to die, get frozen and be brought back to life.

In fact, I am not opposed to death. I would rather not age and become a burden to others however.

Most likely: tomorrow will be pretty much like today, and so on every day. I thought we were supposed to have flying cars by 2010.

By and large, science-fiction authors have a poor record at predicting the future. So if you look at science-fiction novels or TV shows from 1980 or earlier, they totally missed some important developments… and predicted other silly things instead.

So the future will not look like a science-fiction novel or movie.

I would like to see wetware connecting directly to human nerves/brain. Cyberpunk, yes, but helpful for many people (e.g. blind people). Still very far in the future as well. Things happen to be not that easy…

Evidently, even if you got rid of aging, people would still die of cancer and other diseases.

This being said…

Few people die of cancer in their 20s. The reason so many people die of heart attacks, Alzheimer’s and cancer is aging. Aging makes you weak and frail… Your immune system fails and you can no longer fight cancer as efficiently.

On the other hand, if you were to cure cancer, you would not even add 5 years to our lifespan.

So while it might be nice to cure cancer, it would be far more powerful to cure aging.

The thing is… we know a lot of cancer and how to treat it… while we barely know how to start addressing aging… so that is why we focus so much of our effort on cancer… and we must continue the fight against cancer… absolutely… however, it seems clear that medicine will eventually open new fronts in the war against death as our technology and knowledge improves.

I suspect we may never entirely defeat cancer… but by keeping people “super” healthy, we can make it very improbable that a cancer kills you.

On the SciFi aging point: Robert Heinlein had defeating aging as a theme in many of his books. In societies where some characters could defeat againg but the ability was not widespread they had to hide the fact from the rest of society through various methods. Interestingly, you could look at societal taboos as a theme throughout Heinlein’s books.

I’m curious where did you find that naked mole rats do not age ? It is true that they do not get cancer, do not feel pain and live up to 30 times longer that other rats, but they do die eventually, even in the lab.

Bryant: Nexus 6. Roy Batty. Incept date 2016. Combat model. Optimum self-sufficiency. Probably the leader. This is Zhora. She’s trained for an off-world kick-murder squad. Talk about beauty and the beast, she’s both. The fourth skin job is Pris. A basic pleasure model. The standard item for military clubs in the outer colonies. They were designed to copy human beings in every way except their emotions. The designers reckoned that after a few years they might develop their own emotional responses. You know, hate, love, fear, anger, envy. So they built in a fail-safe device.
Deckard: Which is what?
Bryant: Four year life span.

Naked mole rats eventually age in a way that leads to a quick death, but not in a manner that is comparable to us. They remain young and healthy almost until the very end.

So it is better than you make it out to be in the following sense. I do not know that they live 30 times longer than other rats… but they do live quite a bit longer… Yet, and that is the most important part, they spend a greater fraction of their lives in perfect health. By analogy, they are like we would be if at 80, you could go out in a bar, pick up a good looking lad, get pregnant and have kids *as if you were 20*.

The problem with aging is not death per se. The problem with aging is that it causes us to have cancer, hearth attack, to lose our muscles, our memory, to get Alzheimer’s…

These are the things we are after. So far, medical researchers have been trying to fight the diseases themselves… but I think that there is increased recognition that the real cause of these diseases is aging and that we should do something about it. (This is Google’s Calico research agenda.)

More generally, naked mole rats certainly do die, and so do lobsters and turtles and whales, and so would we if we defeated aging. Defeating aging is not about defeating death.

The goal of most scientists involved in anti-aging research is not to achieve an infinite lifespan. The goal is to keep us young and healthy for almost all of our lives… like naked mole rats.

If we could do that, it is evident that the benefits would be enormous. People could keep being productive until near their death. We would drastically reduce the cost of health care.

My prediction is that we shall have the means to achieve just that in about 40 years. (Kurzweil predicts 20 years or so, but I think it is too optimistic.)

But we will still die… The goal is to increase our “healthspan”.

Of course, if we could defeat aging, we could also live longer.

To put it differently, the dream is that we become like mole rats… yes, we die… but we are mostly free of age-related disease…

It was only a dream a century ago… but right now, it has become a credible scientific (and business) goal. We have no idea yet how to realize it, but the clues are piling up.

Thank you Daniel, very interesting observations. I spent entire day reading about naked mole rats and I hope that one day our bodies will be modified to live a long and healthy life, just like naked mole rats. I’m pretty confident though that it won’t happen the next 50 years. May be our kids will experience it.

You are wrong. Conceptually, it is very easy to defeat death. Back up your mindfile each PM and, in the event of a “hardware crash” (AKA death), get your best friend to boot up a cyborg with your mindfile. Viola! You have lost a day’s memory, but are still walking around. I often do that on a Friday night/Saturday morning!

A great article which goes along pretty much with my way of thinking because as I see it there are five technologies which will ultimately lead to radical life extension during the course of this century, these are advanced Biotechnology, Nanotechnology, Advanced Robotics, Genetics and Robust Artificial Intelligence often just referred to just as AI, the effect these technologies will have on life extension differs greatly but my guess is that there are two potential approaches which are likely to come to fruition first, one is SENS which is biotechnology the other is a combination of robust artificial intelligence combined with whole brain emulation. Whole brain emulation is where the brain is uploaded to a digital medium and increasingly enhanced and replaced with non biological components until it reaches a stage where the non biological components can model the biological part so accurately the original brains loss would be irrelevant from a functional perspective. Personally I feel the outcome long term will ultimately be a combination of the five, the crucial point is that each of these technologies individually has the potential to get us to where we need to go. What this means is that for the development of radical life extension to fail all of these technologies must also fail and that simply won’t happen so my guess is we will reach the stage of having a decisive level of control over the aging process within 20/30 years. We must also factor in that there is also a possibility that we could find a faster route and that treatments to lengthen telomeres might have a greater benefit than assumed. Clearly lengthening the telomeres in certain cells through temporary activation of telomerase through a drug developed for the purpose, or maybe permanently by gene therapy could be interesting. The implications for tissue engineering are interesting too but it is not even certain whether the relationship between telomeres and aging is causal so that again is speculative. It’s possible the shortening is a consequence of aging and not a cause. Nevertheless the implications of combined stem cell and lengthened telomeres could mean we can greatly improved our abilities regarding biomedical repairs.

my guess is we will reach the stage of having a decisive level of control over the aging process within 20/30 years.

That sounds a tad optimistic to me. But what do I know?

We must also factor in that there is also a possibility that we could find a faster route and that treatments to lengthen telomeres might have a greater benefit than assumed.

Maybe, but we do not know how to safely extend telomeres reliably. There are signs however that we can extend our telomeres in some cells by controlling stress and eating well, though this evidently does not reverse aging.

but it is not even certain whether the relationship between telomeres and aging is causal so that again is speculative. It’s possible the shortening is a consequence of aging and not a cause.

I agree 20/30 years would be very ambitious to prevent the aging from arising but I feel confident we will be able to apply effective rejuventive interventions to remove the majority of the damage that arises whilst not impacting how it is laid down and when I say that I am talking perhaps 2/3rds and probably not more but it should be enough to buy 20+ years of extra life expectancy,

Let me add also my own argument from authority: De Grey’s theory is *not* mainstream.

And about the name “Cambridge”… Aubrey does have a PhD, but he never held an academic position. Granted, de Grey was lucky to be independently wealthy. He did not need the job. Still, that is not exactly an endorsement.

De Grey has not, as far as I can tell, conducted actual bench research himself.

His PhD contribution was a theory. It is unclear whether this theory is even falsifiable.

My attention was just drawn to this thread. Daniel, let me clarify a few points:

– You are correct that I have had no more experience of bench research than, for example, Francis Crick. It’s only a handicap to making important insights if one lets it be, by being careless.

– You are NOT correct that I was dismissed from my job at Cambridge, nor that I was a computer technician (I actually held a research post). These falsehoods were invented by my ex-boss, Prof. Michael Ashburner, in a single telephone interview that was included in a documentary about me in 2007. Why he decided to defame me remains mysterious, but there it is.

– Most importantly, while you are quite correct that my possession of a PhD from Cambridge does not make SENS mainstream, there are other things which do:

The only part of my position that remains unembraced by the mainstream is the “longevity escape velocity” concept, which appears to elicit such extreme “longevity sticker shock” that those who should know better still seek to distance themselves from it. But I see, with pleasure, that you understand it well.

It is a little odd that you cite the fact that I’m saying the same as I was saying a decade ago as a negative regarding me or SENS. In fact, the reason I’m doing so is becasue I can – because SENS is standing the test of time. It’s no accident that the deprecations SENS was receiving a decade ago have mostly faded away: my critics have learned that their criticisms don’t hold water. And of course we have been publishing at an accelerating rate (see sens.org). The theory that we were simply not designed by evolution to live past 40 is certainly correct (and is not original with you – Medawar first articulted it in 1952), and it (combined with your other point about hacking the genome) is precisely why aging will only succumb to a divide-and-conquer, damage-repair approach such as SENS, which fills the gaps that evolution left open in our anti-aging arsenal.

Personally I am confident that Aubrey de Grey is very much on the right track. The evidence that he is correct is significant and research is increasing supporting much of the research for example removal of senescent cells, stem cell therapies etc but I feel the single most compelling piece of proof to support Aubrey’s theory is that our risk of dying doubles every 7 years or so, for example your risk of death from disease at 21 is double what it was at 14 and at 28 double what it was at 21. Although this doubling every seven years does not become a major problem until you reach say 40 because it starts off at such a low level the growth is exponential meaning it accelerates rapidly with age becoming ever more life threatening. What is abundantly clear is that the only likely cause for this increasing risk of mortality is the accumulation of junk in the body and the genetic damage to our DNA which builds up over time. Aubrey’s theory that if we intervened and removed most of the damage we would make a person biologically younger certainly makes sense.

As far as Aubrey being independently wealthy he inherited a large amount of money a few years back from his mother and gave the vast majority to the SENS foundation so they clearly shows he is a man who is totally committed to getting this job done hence all of us who believe in this cause should contribute to SENS like myself and many others.

I should start by saying that I am very happy that you are doing the work you are doing.

You are NOT correct that I was dismissed from my job at Cambridge, nor that I was a computer technician

I went back in time and edited out my comment.

It is a little odd that you cite the fact that I’m saying the same as I was saying a decade ago as a negative regarding me or SENS. In fact, the reason I’m doing so is becasue I can – because SENS is standing the test of time.

In an active scientific field, one’s views are supposed to progressively change over the years…

The theory that we were simply not designed by evolution to live past 40 is certainly correct (and is not original with you – Medawar first articulted it in 1952)

I would hope that I could not, in a few days, come up with an original theory of aging. 😉

Do you mean that actuarial statistics contradict the wear-and-tear theory? If so, you are incorrect: quite a few models of accumulating damage have been shown to reproduce actuarial data very accurately. In fact, the problem is the reverse of what you suggest – the difficult thing is to find a biologically plausible model that *cannot* be fitted all that accurately to the Gompertz curve – in other words, the literal reading of your statement is indeed true, in that the only way to prove the wear-and-tear theory would be to disprove other biologically plausible theoeies, which cannot be done with actuarial data.

However, there is a deeper problem: are there any other biologically plausible theories in the first place? Some people have suggested that there is some kind of program for aging, i.e. that we have genes that exist for the purpose of driving our physiological decline, but this is very much a minority view, for reasons that I outlined in print recently (PubMed 25902458). As I noted, the idea that evolution lets us age is also not an alternative to the wear and tear theory, but basically just a statement of it in evolutionary language.

“In an active scientific field, one’s views are supposed to progressively change over the years”

You’re making the common error here of confusing science with technology. The reason they change in science is that one does the right experiments to discriminate between hitherto plausible alternative explanations of data, and every so often the results are surprising. In pioneering technology, on the other hand, one only expects to change one’s tune if either (a) new methods come to light that provide easier ways to achieve one’s objective (which has indeed happened a number of times for SENS, such as with CRISPR; such changes are in general too technical to feature in my talks, but they certainly inform our work), or (b) one jumped the gun in one’s initial project proposal and based it on science that ended up being overturned. It increasingly seems that I didn’t do that – that all the science on which SENS was originally based is indeed just as solid as I thought it was.

John – yes, one’s natural image of wear and tear at the macroscopic level is not a particularly faithful description of the damage of aging. However, I don’t feel too bad about using the term (or letting other people use it), because mechanistically it’s the same – it’s changes to the body’s structure and composition that occur as unavoidable (but not irreparable!) side-effects of the body’s normal operation, rather than as any kind of deliberate or preventable process.

it’s accumulation of intra and extracellular aggregates and mutations in the nuclear and mitochondrial DNA that lead to the increased risk of pathology

I do not think we believe that nuclear DNA is affected very much with age. Older twins have still pretty much the same DNA. This is good news (as de Grey has pointed out himself) because fixing broken DNA could be difficult.

As for mitochondrial damage, this study (included at the end of my blog post) seems to invalidate it :

If mitochondrial DNA damage caused deficient cell respiration, we would not be able to revert it with a generous infusion of glycine!

In any case, it looks likely that we will be able to revert mitochondrial “damage” one way or another in the relatively near future if the study on glycine pans out: if the cell can be convinced in vitro to revert the mitochondrial damage using something non-toxic for the body, then it stands to reason we could find a way to do the same in vivo without spending 100 years.

As for intracellular junks, we know that autophagy declines with age. So it seems likely that intracellular junks is a symptom of aging, not a cause. We know that even old cells can still autophage… the body just chooses not to do it… unless we force it (e.g., by caloric restriction). This is maybe good news: we could maybe find the right mix of drugs to encourage our cells to autophage more (without nasty side-effects), and thus make them new again. I expect we shall make progress on this front in next two decades as I think that many anti-aging drugs being considered right now have probably an impact on autophagy.

Extracellular junks seems closely related to the decline of our immune system and is likely a consequence of aging, not a cause.

We probably want to boost our immune system. Again, we are making good progress with immunotherapies so one can be hopeful.

But… I suspect that all of these upcoming therapies will merely slow or delay againg, with some partial reversal. If you go after some of the symptoms of aging, and not aging itself, you will merely alleviate aging, not stop or reverse it.

That is why it is critical to identify the causes of aging so our intervention can be really effective.

“I do not think we believe that nuclear DNA is affected very much with age.”

My position on this is outlined in PubMed 17588643; in brief, we certainly do need to worry about nuclear DNA damage insofar as it causes cancer, but if we can totally control cancer then it’s likely that nuclear DNA damage will not affect our health in oher ways until we’ve lived much longer than anyone lives at present.

“http://www.sciencedaily.com/releases/2015/05/150526085138.htm”

This study is not nearly so interesting as it looks; my colleague Michael Rae has dealt with it in detail as his “Question of the Month” which will appear in our June newsletter within the next few days. Subscribe here:

“As for intracellular junks, we know that autophagy declines with age. So it seems likely that intracellular junks is a symptom of aging, not a cause”

Careful with this. It’s easy to forget that autophagy is not a junk-degradation process, but merely a junk-relocation process: it moves stuff from the cytoplasm into the lysosome, and that’s all. So if the lysosome is not succeeding in destroying the junk it receives, a “traffic jam” builds up that means autophagy is no longer useful. As you say, autophagy itself is not impaired, so if we can get rid of the lysosomal junk it will probably recover automatically – but we won’t get rid of lysosomal junk with “the right mix of drugs”.

“Extracellular junks seems closely related to the decline of our immune system and is likely a consequence of aging, not a cause.”

Actually, the relevant component of the immune system (macrophages and microglia) does not decline noticeably with age. We do want to boost other parts of our immune system, yes, and yes we can be hopeful (though you are on the wrong track when you mention immunotherapies – they are all about making the immune system do the right thing, not reactivating it generally).

“If you go after some of the symptoms of aging, and not aging itself, you will merely alleviate aging, not stop or reverse it. That is why it is critical to identify the causes of aging so our intervention can be really effective.”

This statement is hard to interpret. What is this mysterious thing “aging itself” that you refer to? It is more instructive to avoid the word “aging” and just focus on the order of events. Which changes to the body (at the molecular and cellular level) happen throughout life (albeit maybe at an accelerated rate later in life), and which ones only happen late in life? If you’re saying that we should be attacking the former rather than the latter, i.e. (in SENS terminology) damage rather than pathology, you’re absolutely right. But you seem to think we have not yet identified the “causes of aging” as you call them, whereas (as I pointed out earlier in this thread) not only did I enumerate them in SENS, but also others have echoed this classification in the “Hallmarks of Aging” paper more recently. Aging is simply not mysterious any more (see PubMed 12111727). Alternatively, if you actually mean that (again using SENS terminology) we should be going after metabolism rather than damage,
i.e. stopping our bodies from creating damage in the first place, then you need to make a proper case for why repairing damage is not going to reverse aging – and you have not yet made any attempt to do that.

Let me illustrate what I have in mind. Hormone levels are all out of range as you grow old.

How do you fix that?

I guess that the thought is that the seven repair pathways of SENS will give us back our youthful hormonal levels. But maybe not because in Time to Talk SENS, de Grey et al. advocate hormone therapy.

So isn’t that interesting? Elsewhere, de Grey’s seven sources of damages are presented as an exhaustive model of aging. Fix these things and you are youthful. Well… no, not quite, your hormones will still be out of whack. Oh well, just go on hormonal therapy.

So this means that if you take a 50-year-old man and apply a SENS therapy (by spending, say, a month in a specialized hospital), by de Grey’s own admission, you will not have a youthful man. Unlike the 30-year-old man, he will need to be hormonal theory… and I suspect many other things.

Of course, I would take the SENS therapy over the alternative… but hormonal therapy is clearly a consequence, not the cause. So you will be treating the symptom, not the cause. What is the cause of hormonal imbalance and how do we fix that instead? We do not know. I mean, I think that it is rooted in the fact that our genes did not care to adjust our hormones in old age… but I have not seen any plan to reverse that.

What is apparent is that there is a clock running. (Or many clocks but they appear somewhat synchronized.) Your body shuts down sex hormone production gradually. The thymus gland also shrinks…

As far as I know, we do not know what this clock is. It seems evident that the thymus does not shrink due to “wear and tear”… your hormones do not suffer from “wear and tear”… there is a clock…

Presumably, we could stop or revert this clock.

I personally think that if we could do this, many of the symptoms of aging would reverse themselves. Homeostasis would kick in stronger.

But even if that is not true, what is apparent is that SENS will not reset this clock.

At a minimum, and you should be frank about this, under a best-scenario with SENS, your testicles will shrink to nothing like your thymus.

Evidently, what we would want is for our own body to keep on producing healthy hormones.

Ok. So maybe we achieve something quite acceptable with nanotechnology that can emulate youthfulness… fine… but we are not in a damage-and-repair model anymore. We are in the Kurzweil model where we all become cyborgs in old age.

I am fine with becoming a cyborg… but that is not in the SENS literature…

I do not see the hormone issue as in any way insurmountable because current progress in technology will address these and other issues such as Thymus rejuvenation which is something SENS is already working on see http://sens.org/research/research-blog/first-glimpse-thymic-rejuvenation . Personally I am not a great fan of hormone therapy or balancing unless its low T etc but the evidence suggests even with our limited knowledge (probably an understatement in this area!) significant results are achievable see http://www.cenegenics.com but my concern is whether there are long term side effects etc in light of our current degree of understanding.

Thanks. We’re making good progress here, though I do rather wish you would get out of the habit of writing in a tone that implies you are sure I won’t have good answers to your objections.

“Hormone levels are all out of range as you grow old. How do you fix that?”

By fixing the glands that secrete them, using the seven SENS methods.

“But maybe not because in Time to Talk SENS, de Grey et al. advocate hormone therapy.”

You’re quite right that in that first paper, and indeed in my next couple of overviews of SENS, there were nine categories. But in about 2003 I realised that the extra two, namely hormone changes and immune decline, should not be included, because they could be described much better using the other seven. Note, however, that even back at the start I was proposing quasi-glands (“genetically engineered muscle”), not hormone therapy.

See above.

“The thymus gland also shrinks… It seems evident that the thymus does not shrink due to wear and tear”

Actually, loss of cells in the thymus seems to be just like loss of cells elsewhere – caused by oxidative damage and such like. The only curious thing is that it happens so early in life – but that’s not a mystery either: it is a consequence of the way the adaptive immune system works, i.e. the creation of a massively diverse arsenal of cells pre-set to attack particular future antigens, Those cells don’t decline in diversity to a problematic degree until about the same age that other systems decline to a problematic degree, so the thymus doesn’t need to be maintained beyond early adulthood – it has done all that’s needed for a currently plausible lifetime. In aging this is a problem, of course, and that’s why we’re funding a project to build a new thymus – but it’s squarely within a SENS category (stem cell therapy for cell loss).

“What is apparent is that there is a clock running. (Or many clocks but they appear somewhat synchronized. … As far as I know, we do not know what this clock is. … what is apparent is that SENS will not reset this clock. ”

That depends what you mean by “clock” (another word that is overused in this field, rather like “aging itself”). If all you mean is this:

“At a minimum, and you should be frank about this, under a best-scenario with SENS, your testicles will shrink to nothing like your thymus.”

then as I hope you now see, that is incorrect. SENS incorporates restoration of cell number in whatever organs lose cells – the thymus, the substantia nigra, the sinus node of the heart, the ovary, anywhere that matters. Not sure that testicles need this, as testicular stem cells work quite well in old age, but it’s just as doable there as anywhere else – and this is all still SENS, plain and simple.

I know this is an old post, but I wonder how this would affect younger generation and inequality? If people would stay in perfect physical and mental shape up until the old age, wouldn’t that give them a massive advantage over the younger folks? Youth unemployment is already a big problem in our current economy where good skills increasingly matter. In this situation it’s the old who would have to pay for the education and the living expenses of the young generation either directly as their parents or indirectly via taxes. And pensions would become redundant. You’d be expected to work till the very death or until you have enough savings to last you till the “cut off” time. And making savings likely won’t be easier than it is now because, despite more time and energy, wealth is always a relative thing – you can do better now, but so can your peers.

You’d be expected to work till the very death (…) And making savings likely won’t be easier than it is now because, despite more time and energy, wealth is always a relative thing – you can do better now, but so can your peers.

That’s easily solved. Give people a choice.

Either you get no medical therapies, and so you are likely to be sick by the time you are 65 (arthritis, diabetes, incontinent, memory loss, hearing loss…) and dead by the time you are 80; but you get to keep a pension.

Or else, if you prefer, you forgo your pension and get to remain healthy and young looking.

If people would stay in perfect physical and mental shape up until the old age, wouldn’t that give them a massive advantage over the younger folks?

This could be arranged. Divide the world into different countries.

In some, it just like now, you get old, sick and you die, diminished. In these countries, the 20-something are much better off relatively speaking to the 80-something who are all diminished.

Or else, if you prefer, you go live in a country where you receive top-notch medical care and never grow old and frail. Sadly, in these countries, the 80-something folks are just as fresh as the 20-something folks.

You choose, freely, which country you want to go live in.

In this situation it’s the old who would have to pay for the education and the living expenses of the young generation either directly as their parents or indirectly via taxes.

Which is much less of a burden than to care for old and sick people.

And pensions would become redundant.

If you live in one of the countries where people do not become sick as they age, you can still save for extended vacations.

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